Strongly Suppressing Testosterone during Androgen-Deprivation Therapy Prolongs Survival

June 2013, Vol 4, No 5 - Prostate Cancer

Niagara Falls, Ontario—A secondary analysis of a large study on intermittent versus continuous androgen-deprivation therapy (ADT) has confirmed the importance of aiming for very low testosterone levels in men after they are diagnosed with prostate cancer, according to new data presented at the 2013 Canadian Urological Association annual meeting.

Laurence Klotz, MD, Chief, Division of Urology, Sunnybrook Health Cancer Centre, Toronto, Ontario, was the primary investigator for the PR-7 companion trial, as well as for this new analysis. Dr Klotz and his colleagues determined that maintaining very low testosterone levels nearly halves men’s risk of developing hormone-resistant disease and significantly prolongs their survival time. He commented on these results, “This is one of the most important studies I’ve ever done.”

The PR-7 trial involved 1386 patients with a prostate-specific antigen (PSA) level of >3 ng/mL that persisted for more than 1 year after primary or salvage radiotherapy for localized prostate cancer (Crook JM, et al. N Engl J Med. 2012;367:895-903). Intermittent and continuous ADT were associated with similar rates of survival and with 7-year cumulative rates for prostate cancer mortality.

Two previous small, retrospective studies had suggested that testosterone levels <0.7 ng/mL are associated with prolonged time to prostate cancer progression. But Dr Klotz expressed significant skepticism about the sturdiness of these studies. To de­fin­itively examine the issue, he and his colleagues analyzed data from the first year of the PR-7 trial of 626 men receiving continuous ADT.

They found that having a median testosterone level of ≥1.7 ng/mL was associated with a 1.9-fold increased risk of developing hormone-resistant prostate cancer compared with a testosterone level of <0.7 ng/mL.

Furthermore, the hazard ratio (HR) was 2.8 for time to development of hormonal resistance in the lowest testosterone level group compared with the highest testosterone level group.

Similarly, the patients who had the lowest testosterone levels had an HR of 2.8 for time between castration resistance and death compared with the highest testosterone level group. However, no significant decrease was seen in prostate cancer–related mortality, “probably because of a lack of events,” noted Dr Klotz.

“If you have failure of testosterone suppression, you should consider changing the drug, perhaps adding an antiandrogen,” he concluded. “Testosterone, as well as PSA, should be monitored on a regular basis in these patients.”